Human erythrovirus (parvovirus) B19 (B19) is a common human pathogen. The recent discovery of three genotypes, 1 to 3, raised issues related to the ability of genotype-specific antigens to cross-react with antibodies elicited by other genotypes. This study assessed antibody capture and immunoglobulin G (IgG) cross-reactivity between genotype 1 and genotype 3 recombinant antigens and analyzed the potential gain of adding VP1 protein to VP2 capsid antigen. Plasma samples from genotype 1-or genotype 3-infected populations were blindly tested with blindly prepared reagents. The IgG reactivity was assessed with baculovirus-expressed VP2 or VP1 and VP2 recombinant genotype 1 or genotype 3 proteins in a standardized enzyme immunoassay (EIA). A high degree of agreement (>95%) between EIA results was observed, with Spearman correlation coefficient and kappa reliability coefficient results of >0.95 for samples from the United Kingdom and >0.77 for samples from Ghanaian children, respectively. Most discrepant results were related to equivocal reactivity. The addition of VP1 to VP2 capsids did not significantly impact antibody detection. These data suggest that the currently available genotype-1-based IgG EIA is suitable to detect antibody to B19 genotype 3 in Ghanaian children. However, samples from the Ghanaian adult population exhibited atypical results in the assay, possibly due to the high levels of nonspecific IgG antibodies found in adults living in this region. Within these limitations, the study demonstrates that genotype 1 and genotype 3 antigens are equally effective in detecting either antibody species.Human erythrovirus (parvovirus) B19 (called B19 in this report) is a nonenveloped single-stranded DNA virus (9, 32). B19 causes a range of diseases and conditions in humans, including fifth disease of childhood, fetal death, various forms of anemia, and other conditions (reviewed in reference 38).Three relatively long polypeptides encoded by the virus are two structural proteins (VP1 and VP2) and one nonstructural protein (NS-1) (8, 27). VP1 (781 amino acids [aa]) and VP2 (554 aa) are encoded by the same open reading frame and translated from two differentially spliced messages (25-27). VP1 is identical to VP2 except for a 227-aa N-terminal extension called the VP1 unique region. These two proteins form capsids (diameters, 19 to 25 nm) containing approximately 96% of VP2 and 4% of VP1 (27). In the eukaryotic baculovirus expression system, VP2 protein spontaneously forms virus-like particles that, under electron microscopy, are indistinguishable from the capsid structure of the native virions (4, 17). VP1 protein alone forms these structures very inefficiently, but when cotransfected with VP2-and VP1-containing recombinant baculovirus, chimeric capsids with VP2 and VP1 are produced (4, 17, 37). Up to 41% of VP1 was reported to be possible to incorporate in the capsid (3).The nature of the immune response to the virus is characterized by the predominance of antibodies against structural proteins. Immunoglobulin G (I...